GEN News Highlights

“You go to war with the army you have.” Not necessarily. While a standing army of immune cells may be ill-constituted to fight cancer, it needn’t stay that way. At least, that’s the premise of adoptive cell therapy, a treatment approach that begins with the identification suitable immune cell recruits—immune cells that are capable of responding to a tumor’s mutant proteins. These immune cells, which are called tumor-infiltrating lymphocytes (TILs), may be called to action if needed, when the body becomes a cancer battleground.

The TILs are collected from a patient afflicted with cancer. Then, the best TILs are grown in the laboratory to produce large populations that are infused into the patient. Then, freshly deployed, the TILs stage a counterattack.

Such are the essentials of adoptive cell therapy. It has been used with some success against melanomas. But, until recently, it hadn’t been tried against epithelial cell cancers, which account for 80% of all cancers, including those that develop in the digestive tract, lung, pancreas, bladder, and other areas of the body. Before adoptive cell therapy could be tried against an epithelial cell cancer, medical scientists were left to wonder whether their plan would survive contact with the enemy.

Reports from the front, however, are encouraging. Scientists at the National Cancer Institute (NCI) have provided evidence that a T-cell response against a mutant protein can be harnessed to mediate regression of a metastatic epithelial cancer. These scientists, led by Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research, presented the details of their work May 9 in Science, in an article entitled “Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.”

In this study, Dr. Rosenberg and his team analyzed TILs from a patient with bile duct cancer that had metastasized to the lung and liver and had not been responsive to standard chemotherapy. “We used a whole-exomic-sequencing-based approach to demonstrate that TILs from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer,” wrote the authors. “After adoptive transfer of [42.4 billion] TILs containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease.”

When the patient’s disease eventually progressed, after about 13 months, she was re-treated with adoptive cell therapy in which 95% of the transferred cells were mutation-reactive T cells, and she experienced tumor regression that was ongoing as of the last follow up (six months after the second T-cell infusion).

This result led the authors to conclude that their approach showed promise in clearing a major hurdle for the success of immunotherapies for gastrointestinal and other cancers—the apparent low frequency of tumor-reactive T cells. “The strategies reported here could be used to generate a T-cell adoptive cell therapy for patients with common cancers,” said Dr. Rosenberg. “The method we have developed provides a blueprint for using immunotherapy to specifically attack sporadic or driver mutations, unique to a patient’s individual cancer.”

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